The present invention, in some embodiments thereof, relates to anti-CEACAM1 antibodies, hybridoma cells producing same and methods of using same.
The transmembrane protein CEACAM1 [also known as biliary glycoprotein (BGP), CD66a and C-CAM1] is a member of the carcinoembryonic antigen family (CEA) that also belongs to the immunoglobulin superfamily. CEACAM1 interacts with other known CD66 proteins, including CD66a, CD66c, and CD66e proteins. It is expressed on a wide spectrum of cells, ranging from epithelial cells to those of hemopoietic origin (e.g. immune cells).
Many different functions have been attributed to the CEACAM1 protein. It was shown that the CEACAM1 protein exhibits anti-proliferative properties in carcinomas of colon, prostate, as well as other types of cancer. Additional data support the central involvement of CEACAM1 in angiogenesis and metastasis. CEACAM1 also plays a role in the modulation of innate and adaptive immune responses. For example, CEACAM1 was shown to be an inhibitory receptor for activated T cells contained within the human intestinal epithelium [see WO99/52552 and Morales et al. J. Immunol. 163 (1999), 1363-1370]. Additional reports have indicated that CEACAM1 engagement either by TCR cross-linking with mAb or by Neisseria gonorrhoeae Opa proteins inhibits T cell activation and proliferation.
Melanoma is a malignancy of pigment-producing cells (melanocytes), responsible for 75% of skin cancer-related incidence worldwide, mainly due to extensive metastasis. Metastatic melanoma (MM) responds feebly to most anticancer regimens and overall survival mean for patients with MM is 8.5 months. CEACAM1 is rarely expressed by normal melanocytes, but frequently found on melanoma cells. CEACAM1 expression on primary cutaneous melanoma lesions strongly predicts the development of metastatic disease with poor prognosis. Moreover, increased CEACAM1 expression was observed on NK cells derived from some patients with metastatic melanoma compared with healthy donors.
WO2007/063424 and U.S. Patent Application No. 20070110668 disclose methods for regulating the immune system, and in particular methods for the regulation of a specific immune response, including the regulation of lymphocyte activity. These methods comprise both the negative and positive modulation of CEACAM1 protein function.
U.S. Patent Application No. 20070071758 discloses methods and compositions for the treatment and diagnosis of cancers. Specifically, U.S. Patent Application No. 20070071758 teaches methods and compositions for enhancing the efficacy of tumor-infiltrating lymphocyte (TIL) therapy in the treatment of cancer by negatively modulating the activity of the CEACAM1 protein, such as for example, by using an immunoglobulin specific for CEACAM1.
U.S. Patent Application No. 20080108140 discloses methods of modulating specific immune responses to create a protective immunity in the treatment of autoimmune diseases and diseases requiring the transplantation of tissue. In particular, U.S. Patent Application No. 20080108140 relates to the suppression of immune responses in a targeted fashion, by increasing the functional concentration of the CEACAM1 protein in the target tissue.
U.S. Patent Application No. 20040047858 discloses specific antibodies (i.e. 34B1, 26H7 and 5F4) which are capable of modulating T cell activity via CEACAM1 and uses thereof such as in treating immune response related diseases (e.g. graft versus host disease, autoimmune diseases, cancers etc.).
U.S. Patent Application Nos. 20020028203, 20050169922 and 20080102071 disclose compositions which bind T cell inhibitory receptor molecules and modulate (i.e. enhance or suppress) T cell activity (e.g. cytotoxicity and proliferation), such as biliary glycoprotein binding agents, and methods of using such compositions such as for treatment of diseases (e.g. an autoimmune disease, immunodeficiency, cancer etc.).
Other related art:
5F4 mAb: Regulation of human intestinal intraepithelial lymphocyte cytolytic function by biliary glycoprotein (CD66a) [Morales V M et al., J Immunol. (1999) 163(3): 1363-70].
GM8G5 and 29H2—both available commercially from Abcam Inc. abcamdotcomdotportal.